2v0r
crystal structure of a hairpin exchange variant (LTx) of the targeting LINE-1 retrotransposon endonuclease
Structural highlights
FunctionLORF2_HUMAN Has a reverse transcriptase activity required for target-primed reverse transcription of the LINE-1 element mRNA, a crucial step in LINE-1 retrotransposition. Has also an endonuclease activity that allows the introduction of nicks in the chromosomal target DNA. Cleaves DNA in AT-rich regions between a 5' stretch of purines and a 3' stretch of pyrimidines, corresponding to sites of LINE-1 integration in the genome.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe human LINE-1 endonuclease (L1-EN) is the targeting endonuclease encoded by the human LINE-1 (L1) retrotransposon. L1-EN guides the genomic integration of new L1 and Alu elements that presently account for approximately 28% of the human genome. L1-EN bears considerable technological interest, because its target selectivity may ultimately be engineered to allow the site-specific integration of DNA into defined genomic locations. Based on the crystal structure, we generated L1-EN mutants to analyze and manipulate DNA target site recognition. Crystal structures and their dynamic and functional analysis show entire loop grafts to be feasible, resulting in altered specificity, while individual point mutations do not change the nicking pattern of L1-EN. Structural parameters of the DNA target seem more important for recognition than the nucleotide sequence, and nicking profiles on DNA oligonucleotides in vitro are less well defined than the respective integration site consensus in vivo. This suggests that additional factors other than the DNA nicking specificity of L1-EN contribute to the targeted integration of non-LTR retrotransposons. Determinants for DNA target structure selectivity of the human LINE-1 retrotransposon endonuclease.,Repanas K, Zingler N, Layer LE, Schumann GG, Perrakis A, Weichenrieder O Nucleic Acids Res. 2007;35(14):4914-26. Epub 2007 Jul 10. PMID:17626046[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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